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Type 1 diabetes mellitus (T1D) is a heterogeneous condition. We aimed to study the associations between age and sex with clinical characteristics at the onset of pediatric T1D. A secondary analysis was conducted on data collected retrospectively from 706 children newly diagnosed with T1D at a large tertiary hospital in southeastern USA. Age (stratified across three cohorts from 0.84 to 18.08 years), sex, and their interaction were compared for associations with clinical characteristics of T1D at presentation by multivariable regression analyses and pairwise comparisons. Within the participants (mean age 9.71 (SD 4.10), 48.3 % female, 21.0 % Hispanic, 15.3 % non-Hispanic black and 58.7 % non-Hispanic white), children under 6 years had higher glucose (p<0.001), lower hemoglobin A1c (HbA1c) (p<0.001), and lower C-peptide (p<0.001) than the older age groups. Diabetic ketoacidosis (DKA) was more prevalent in the youngest (p=0.005) and the intermediate-aged cohorts (p=0.005), compared to the oldest group. Among the children with DKA, bicarbonate was lower in the youngest (p<0.001) and middle cohorts (p=0.013), compared to the oldest group. Younger age was associated with higher prevalence of insulin autoantibodies (IAA; p<0.001) and IA-2 autoantibodies (IA-2A; p=0.006). Males had higher glucose (p=0.001), but lower HbA1c (p=0.003), lower C-peptide (p<0.001), and lower GAD autoantibody (GADA) prevalence (p=0.001) than females. There was no significant interaction between age and sex. In children with new onset T1D, younger age and male sex were associated with findings suggestive of more rapid and aggressive T1D preclinical course, including poorer beta-cell function, and distinct islet autoantibody profiles. [ABSTRACT FROM AUTHOR]

Context Misclassification of diabetes type occurs in people with atypical presentations of type 1 diabetes (T1D) or type 2 diabetes (T2D). Although current clinical guidelines suggest clinical variables and treatment response as ways to help differentiate diabetes type, they remain insufficient for people with atypical presentations. Objective This work aimed to assess the clinical utility of 2 polygenic scores (PGSs) in differentiating between T1D and T2D. Methods Patients diagnosed with diabetes in the UK Biobank were studied (N = 41 787), including 464 (1%) and 15 923 (38%) who met the criteria for classic T1D and T2D, respectively, and 25 400 (61%) atypical diabetes. The validity of 2 published PGSs for T1D (PGST1D) and T2D (PGST2D) in differentiating classic T1D or T2D was assessed using C statistic. The utility of genetic probability for T1D based on PGSs (GenProb-T1D) was evaluated in atypical diabetes patients. Results The joint performance of PGST1D and PGST2D for differentiating classic T1D or T2D was outstanding (C statistic = 0.91), significantly higher than that of PGST1D alone (0.88) and PGST2D alone (0.70), both P less than.001. Using an optimal cutoff of GenProb-T1D, 23% of patients with atypical diabetes had a higher probability of T1D and its validity was independently supported by clinical presentations that are characteristic of T1D. Conclusion PGST1D and PGST2D can be used to discriminate classic T1D and T2D and have potential clinical utility for differentiating these 2 types of diseases among patients with atypical diabetes. [ABSTRACT FROM AUTHOR]

Objectives: Type 1 diabetes mellitus (T1D) is a heterogeneous condition. We aimed to study the associations between age and sex with clinical characteristics at the onset of pediatric T1D., Methods: A secondary analysis was conducted on data collected retrospectively from 706 children newly diagnosed with T1D at a large tertiary hospital in southeastern USA. Age (stratified across three cohorts from 0.84 to 18.08 years), sex, and their interaction were compared for associations with clinical characteristics of T1D at presentation by multivariable regression analyses and pairwise comparisons., Results: Within the participants (mean age 9.71 (SD 4.10), 48.3 % female, 21.0 % Hispanic, 15.3 % non-Hispanic black and 58.7 % non-Hispanic white), children under 6 years had higher glucose (p<0.001), lower hemoglobin A1c (HbA1c) (p<0.001), and lower C-peptide (p<0.001) than the older age groups. Diabetic ketoacidosis (DKA) was more prevalent in the youngest (p=0.005) and the intermediate-aged cohorts (p=0.005), compared to the oldest group. Among the children with DKA, bicarbonate was lower in the youngest (p<0.001) and middle cohorts (p=0.013), compared to the oldest group. Younger age was associated with higher prevalence of insulin autoantibodies (IAA; p<0.001) and IA-2 autoantibodies (IA-2A; p=0.006). Males had higher glucose (p=0.001), but lower HbA1c (p=0.003), lower C-peptide (p<0.001), and lower GAD autoantibody (GADA) prevalence (p=0.001) than females. There was no significant interaction between age and sex., Conclusions: In children with new onset T1D, younger age and male sex were associated with findings suggestive of more rapid and aggressive T1D preclinical course, including poorer beta-cell function, and distinct islet autoantibody profiles., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Introduction: There are known disparities in diabetes complications by race and ethnicity. Although diabetes subgroups may contribute to differential risk, little is known about how subgroups vary by race/ethnicity.Methods: Data were pooled from 1293 (46% female) participants of the Mediators of Atherosclerosis in South Asians Living in America (MASALA) and the Multi-Ethnic Study of Atherosclerosis (MESA) who had diabetes (determined by diabetes medication use, fasting glucose, and glycated hemoglobin [HbA1c]), including 217 South Asian, 240 non-Hispanic white, 125 Chinese, 387 African American, and 324 Hispanic patients. We applied k-means clustering using data for age at diabetes diagnosis, body mass index, HbA1c, and homeostatic model assessment measures of insulin resistance and beta cell function. We assessed whether diabetes subgroups were associated with race/ethnicity, concurrent cardiovascular disease risk factors, and incident diabetes complications.Results: Five diabetes subgroups were characterized by older age at diabetes onset (43%), severe hyperglycemia (26%), severe obesity (20%), younger age at onset (1%), and requiring insulin medication use (9%). The most common subgroup assignment was older onset for all race/ethnicities with the exception of South Asians where the severe hyperglycemia subgroup was most likely. Risk for renal complications and subclinical coronary disease differed by diabetes subgroup and, separately, race/ethnicity.Conclusions: Racial/ethnic differences were present across diabetes subgroups, and diabetes subgroups differed in risk for complications. Strategies to eliminate racial/ethnic disparities in complications may need to consider approaches targeted to diabetes subgroup. [ABSTRACT FROM AUTHOR]

Aims: Microvascular complications' risk differs between people with latent autoimmune diabetes in adults (LADA) and people with type 2 diabetes. We aimed to investigate whether the prevalence of cardiac autonomic neuropathy, a life‐threatening complication of diabetes, also varies depending on diabetes type. Methods: In this cross‐sectional study, 43 adults with LADA, 80 with type 1 diabetes and 61 with type 2 diabetes were screened for cardiac autonomic neuropathy with recommended tests. Logistic regression models were used to test differences between diabetes types adjusting for confounders. Results: Cardiac autonomic neuropathy was diagnosed in 17 (40%) participants with LADA, 21 (26%) participants with type 1 diabetes and 39 (64%) participants with type 2 diabetes (p < 0.001). The odds ratio (OR) for cardiac autonomic neuropathy in type 1 diabetes and in type 2 diabetes compared to LADA were 0.54 (95% CI: 0.25–1.20, p‐value: 0.13) and 2.71 (95% CI: 1.21–6.06, p‐value 0.015) respectively. Smoking (adjOR 3.09, 95% CI: 1.40–6.82, p‐value: 0.005), HDL cholesterol (adjOR 0.29, 95% CI: 0.09–0.93, p‐value: 0.037) and hypertension (adjOR 2.11, 95% CI: 1.05–4.24, p‐value: 0.037) were independent modifiable risk factors for cardiac autonomic neuropathy. Differences among diabetes types did not change after correction for confounders. Conclusions: This is the first study offering a comparative evaluation of cardiac autonomic neuropathy among LADA, type 1 and type 2 diabetes, showing a lower risk of cardiac autonomic neuropathy in LADA compared to type 2 diabetes and similar compared to type 1 diabetes. This disparity was not due to differences in age, metabolic control or cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Physiological plasticity enables homeostasis to be maintained in biological systems, but when such allostasis fails, then disease can develop. In a new population-based study by Rolandsson et al (10.1007/s00125-019-05016-3), autoimmunity, defined by an immunogenotype, predicted adult-onset non-insulin requiring diabetes. Type 1 diabetes is no longer viewed as a disease confined to children, with a significant proportion, maybe the majority, presenting in adulthood. Such cases masquerade as type 2 diabetes and their identification has clinical utility. Nevertheless, in this study, autoimmunity had a limited effect on the overall risk of adults developing diabetes. [ABSTRACT FROM AUTHOR]

Context: Misclassification of diabetes type occurs in people with atypical presentations of type 1 diabetes (T1D) or type 2 diabetes (T2D). Although current clinical guidelines suggest clinical variables and treatment response as ways to help differentiate diabetes type, they remain insufficient for people with atypical presentations., Objective: This work aimed to assess the clinical utility of 2 polygenic scores (PGSs) in differentiating between T1D and T2D., Methods: Patients diagnosed with diabetes in the UK Biobank were studied (N = 41 787), including 464 (1%) and 15 923 (38%) who met the criteria for classic T1D and T2D, respectively, and 25 400 (61%) atypical diabetes. The validity of 2 published PGSs for T1D (PGST1D) and T2D (PGST2D) in differentiating classic T1D or T2D was assessed using C statistic. The utility of genetic probability for T1D based on PGSs (GenProb-T1D) was evaluated in atypical diabetes patients., Results: The joint performance of PGST1D and PGST2D for differentiating classic T1D or T2D was outstanding (C statistic = 0.91), significantly higher than that of PGST1D alone (0.88) and PGST2D alone (0.70), both P less than .001. Using an optimal cutoff of GenProb-T1D, 23% of patients with atypical diabetes had a higher probability of T1D and its validity was independently supported by clinical presentations that are characteristic of T1D., Conclusion: PGST1D and PGST2D can be used to discriminate classic T1D and T2D and have potential clinical utility for differentiating these 2 types of diseases among patients with atypical diabetes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Abstract: Metabolic disorders present a public health challenge of staggering proportions. In diabetes, there is an urgent need to better understand disease heterogeneity, clinical trajectories, and related comorbidities. A pressing and timely question is whether we are ready for precision medicine in diabetes. Some biological insights that have emerged during the last decade have already been used to direct clinical decision making, especially in monogenic forms of diabetes. However, much work is necessary to integrate high‐dimensional explorations into complex disease architectures, less penetrant biological alterations, and broader phenotypes, such as type 2 diabetes. In addition, for precision medicine to take hold in diabetes, reproducibility, interpretability, and actionability remain key guiding objectives. In this review, we examine how mounting data sets generated during the last decade to understand biological variability are now inspiring new venues to clarify diabetes nosology and ultimately translate findings into more effective prevention and treatment strategies. [ABSTRACT FROM AUTHOR]